Arvi Rauk

On the calculation of multiplet energies by the hartree-fock-slater method

It is shown that a consistent application of the p1/3 approximation of the Hartree-Fock-Slater method requires the use of one specific procedure, the sum method, for the calculation of the energy Es1of singlet excited states of closed shell molecules. Further, Es1is found to be in reasonable agreement with experiment for a number of molecules, contrary to the energy Es2obtained according to another method discussed in the literature. The calculation of other multiplet splittings than singlet-triplet in the Hartree-Fock-Slater method is also considered.

On the calculation of bonding energies by the Hartree Fock Slater method

A transition state method has been proposed for the calculation of bonding energies and bond distances within the Hartree Fock Slater Method. Calculations on a number of diatomic molecules and a few transition metal complexes show better agreement with experiment than corresponding Hartree Fock results. The proposed transition state method gives a direct connection between bond orders and bonding energies.

The electronic structures of tetrahedral oxo-complexes. The nature of the “charge transfer” transitions

Abstract The electronic structures of MnO − 4 , MnO 2− 4 , MnO 3− 4 , CrO 2− 4 , CrO 3− 4 , VO 3− 4 , RuO 4 , RuO − 4 , RuO 2− 4 , TcO − 4 and MoO 2− 4 have been investigated using the Hartree-Fock-Slater Discrete Variational Method. The calculated ordering of the valence orbitals of all the comlexes is: t 1 , 4t 2 , 3a 1 , 1c, 3t 2 , with t 1 the orbital of highest energy. The calculated single transition energies are in good agreement with experimental values and indicate the uniform assignment: t 1 → 2e( v 1 ), 4t 2 → 2e( v 2 ). t 1 → 5t 2 ( v 3 ), and 4t 2 → 5t 2 ( v 4 ). A/D values, calculated from the theory of magnetic circular dichroism (MDC) also support this assignment. Population analyses reveal that all complexes, whether d 0 , d 1 or d 2 , have d-orbital populations close to those of the corresponding M 2+ ions in which two electrons have been removed from the ( n + 1)s orbital of M. This is also true of the excited states, such as t 1 → 2e and 4t 2 → 2e, where a transfer of charge from the ligands to the metal has previously been assumed. It is shown that, instead of a transfer of charge from ligands to metal, electronic excitation consists of a rearrangement of electron density both at the ligands and at the metal.

Why is the amyloid beta peptide of Alzheimer's disease neurotoxic?

In this article, we support the case that the neurotoxic agent in Alzheimers disease is a soluble aggregated form of the amyloid beta peptide (Abeta), probably complexed with divalent copper. The structure and chemical properties of the monomeric peptide and its Cu(ii) complex are discussed, as well as what little is known about the oligomeric species. Abeta oligomers are neurotoxic by a variety of mechanisms. They adhere to plasma and intracellular membranes and cause lesions by a combination of radical-initiated lipid peroxidation and formation of ion-permeable pores. In endothelial cells this damage leads to loss of integrity of the blood-brain barrier and loss of blood flow to the brain. At synapses, the oligomers close neuronal insulin receptors, mirroring the effects of Type II diabetes. In intracellular membranes, the most damaging effect is loss of calcium homeostasis. The oligomers also bind to a variety of substances, mostly with deleterious effects. Binding to cholesterol is accompanied by its oxidation to products that are themselves neurotoxic. Possibly most damaging is the binding to tau, and to several kinases, that results in the hyperphosphorylation of the tau and abrogation of its microtubule-supporting role in maintaining axon structure, leading to diseased synapses and ultimately the death of neurons. Several strategies are presented and discussed for the development of compounds that prevent the oligomerization of Abeta into the neurotoxic species.

Computational studies of Cu(II)[peptide] binding motifs: Cu[HGGG] and Cu[HG] as models for Cu(II) binding to the prion protein octarepeat region.

Abstract. The binding of Cu(II) to the prion protein is investigated by computations at the B3LYP level of theory on models of the octarepeat domain of the prion protein. The models incorporate the functionality of the glycine (G) and histidine (H) residues which occur in the octarepeat domain, PHGGGWGQ. The copper complexes are designated Cu[HG] and Cu[HGGG]. Coordination to the metal via the imidazole ring of the histidine, the amide carbonyl groups, and the backbone nitrogen atom of the amide groups were examined, as well as several protonation/deprotonation states of each structure. EPR and CD titration experiments suggest that the octarepeat segments of the unstructured N-terminal domain of prion protein can bind Cu(II) in a 1:1 Cu-to-octarepeat ratio. The results identify the extent to which the Cu(II) facilitates peptide backbone deprotonation, and the propensity of binding in the forward (toward the C-terminus) direction from the anchoring histidine residue. A plausible mechanism is suggested for changing from amide O-atom to deprotonated amide N-atom coordination, and for assembly of the observed species in solutions of Cu[PrP] and truncated models of it. A structure is proposed which has the N2O2 coordination pattern for the minor component observed experimentally by EPR spectroscopy for the Cu[HGGG] model. The most stable neutral Cu[HGGG] structure found, with coordination environment N3O1, corresponds to that observed for Cu[HGGGW] and Cu[HGGG] both in the solid state and as the major component in solution at neutral pH. Electronic supplementary material to this paper can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00775-002-0386-7.

The computation of oscillator strengths and optical rotatory strengths from molecular wavefunctions. The electronic states of H2O, CO, HCN, H2O

Abstract A method is described for the determination of excited state wavefunctions from which transition moments over one electron operators can readily be det

Mechanism of Hydrogen Peroxide Production by Copper-Bound Amyloid Beta Peptide: A Theoretical Study

The amyloid beta peptide (Abeta) of Alzheimers disease evolves hydrogen peroxide in vitro in the presence of Cu(II), external reducing agents, and molecular oxygen, without producing detectable amounts of the one-electron reduced intermediate, superoxide, O(2)(-*). The mechanism of this process was examined by ab initio computational chemistry techniques in systems that model the binding of Cu(II) to the His13His14 fragment of Abeta. The catalytic cycle begins with the reduction of the most stable Cu(II) complex to the most stable Cu(I) complex. This Cu(I) complex forms a Cu(II)-like adduct with (3)O(2) that cannot dissociate in water to yield O(2)(-*). However, it can be reduced by proton-coupled electron transfer to an adduct between HOO(-) and the Cu(II)-like complex, which in turn can be protonated. The protonated complex decomposes to yield H(2)O(2) by an associative-dissociative mechanism, thus completing the cycle.

Ab initio model studies of copper binding to peptides containing a His–His sequence: relevance to the β-amyloid peptide of Alzheimer’s disease

Two of the defining hallmarks of Alzheimer’s disease (AD) are deposits of the β-amyloid peptide, Aβ, and the generation of reactive oxygen species, both of which may be due to the Aβ peptide coordinating metal ions. The Cu2+ concentrations in cores of senile plaques are significantly elevated in AD patients. Experimental results indicate that Aβ1–42 in particular has a very high affinity for Cu2+, and that His13 and His14 are the two most firmly established ligands in the coordination sphere of the copper ion. Quantum chemical calculations using the unrestricted B3LYP hybrid density functional method with the 6–31G(d) basis set were performed for geometries, zero point energies and thermochemistry. The effects of solvation were accommodated using the CPCM method. The enthalpies were calculated with the 6–311+G(2df,2p) basis set. Calculations show that when Cu(H2O)42+ combines with the model compound 1 (3-(1H-imidazol-5-yl)-N-[2-(1H-imidazol-5-yl)ethyl] propanamide) in the aqueous phase, the most stable binding site involves the Nπ atoms of His13 and His14 as well as the carbonyl of the intervening backbone amide group. These structures are fairly rigid and the implications for conformational changes to the Aβ backbone are discussed. In solution at pH=7, Cu2+ promotes the deprotonation and involvement in the binding of the backbone amide nitrogen in a β-sheet like structure. This geometry does not induce strain in the peptide backbone, making it the most likely representation of that portion of the Cu2+–Aβ complex monomer in aqueous solution.

Synthesis and cyclooxygenase inhibitory activities of some N-acylhydrazone derivatives of isoxazolo[4,5-d]pyridazin-4(5H)-ones

In this study, new isoxazolo[4,5-d]pyridazin-4(5H)-one derivatives having an N-acylhydrazone moiety were synthesized. The compounds were tested for their COX inhibitory activities using NS-398 and indomethacine as reference compounds. Although the compounds had an inhibitory profile against both COX-1 and COX-2, most were found to be more selective against COX-2 by a small percentage of inhibition, at the concentration of 50 microM. Docking studies were done to understand the interactions of the tested compounds with the active site of COX-2. It was observed that the compounds fit into, and interacted with, the hydrophobic parts which are common in the active pocket of COX-1 and COX-2 enzymes but could not fit to the area which is specific for COX-2 enzyme.

HERON rearrangement of N,N′-diacyl-N,N′-dialkoxyhydrazines — a theoretical and experimental study

Abstract Ab initio calculations at the B3LYP/6–31G* level on N -methoxy- N -dimethylaminoformamide and its rearrangement to methyl formate and 1,1-dimethyldiazene through the HERON reaction, have been carried out in conjunction with an experimental study of the HERON reactions of N , N ′-diacyl- N , N ′-dialkoxyhydrazines. Substituent effects are in accord with the theoretical properties of the transition state and point to an anomerically driven process in which donor groups on the anomeric nitrogen and withdrawing groups on the migrating alkoxy oxygen facilitate the rearrangement process.